Hemostasis analyzer and method

ABSTRACT

A method and device for blood hemostasis analysis is disclosed. A blood sample is displaced to reach a resonant state. The resonant frequency of the blood sample is determined before, during and after a hemostasis process. The changes in the resonant frequency of the blood sample are indicative of the hemostasis characteristics of the blood sample.

FIELD OF THE DISCLOSURE

This disclosure relates generally to blood analysis, and moreparticularly, to a blood hemostasis analyzer and method.

BACKGROUND

Blood is in liquid form when traveling undisturbed in bodilypassageways. However, an injury may cause rapid clotting of the blood atthe site of the injury to initially stop the bleeding, and thereafter,to help in the healing process. An accurate measurement of the abilityof a patient's blood to coagulate in a timely and effective fashion andto subsequent lysis is crucial to certain surgical and medicalprocedures. Also, accurate detection of abnormal hemostasis is ofparticular importance with respect to appropriate treatment to be givento patients suffering from clotting disorders.

Blood hemostasis is a result of highly complex biochemical processesthat transform the blood from a liquid state to a solid state.Characteristics of blood, such as strength of the clot, infer that themechanical properties of the blood are important in determiningcharacteristics rather than the viscosity of the blood when in a liquidstate.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a blood hemostasis analyzer constructedin accordance with the teachings of the instant disclosure.

FIG. 2 is a graph representing hemostasis characteristics of a bloodsample in accordance with the teachings of the instant disclosure.

FIG. 3 is a perspective and exploded sectional view of a container forholding a blood sample in accordance with the teachings of the instantdisclosure.

FIG. 4 is a schematic view of the container of FIG. 3 having therein ablood sample and vibrating the blood sample in accordance with theteachings of the instant disclosure.

FIG. 5 is a schematic view of an analyzer in accordance with theteachings of the instant disclosure.

FIG. 6 is a schematic view of an analyzer in accordance with theteachings of the instant disclosure.

FIG. 7 is a schematic view of an analyzer in accordance with theteachings of the instant disclosure.

FIG. 8 is a perspective view of a first exemplary stand for a bloodhemostasis analyzer constructed in accordance with the teachings of theinstant disclosure.

FIG. 9 is a perspective view of a second exemplary stand for a bloodhemostasis analyzer constructed in accordance with the teachings of theinstant disclosure.

DETAILED DESCRIPTION

Referring to FIG. 1, a blood hemostasis analyzer 10 in accordance withthe teachings of the instant disclosure is generally shown. The analyzer10 operates under the principle that because hemostasis of a bloodsample changes the blood sample from a liquid state to a gel-like state,and the modulus of elasticity of the blood sample controls the naturalfrequency of the blood sample, measuring the changes in the naturalfrequency of the blood sample during hemostasis provides the hemostasischaracteristics of the blood sample. In keeping with this principle, thedisclosed blood hemostasis analyzer 10 measures the changes in thefundamental natural frequency of a blood sample during hemostasis andlysis processes to provide hemostasis characteristics of the bloodsample. To practice the foregoing principal, the analyzer 10 generallyincludes a container 12 for holding a blood sample 14, a shaker 16 fordisplacing the container 12 to thereby excite the blood sample 14 to aresonant vibration, and a sensor 18 for measuring the resultingamplitude of the blood sample 14.

An exemplary method by which the disclosed blood hemostasis analysis isperformed will now be described. Vibration of a liquid at resonanceclosely resembles sloshing, which is analogous to the motion of apendulum. Accordingly, as blood transitions from a liquid state to agel-like state and possibly to a solid state during clotting, thefundamental natural frequency of the blood increases. The disclosedexemplary method measures the changes in the fundamental naturalfrequency of the blood sample 14 during hemostasis/clotting and lysisprocesses.

Initially, a blood sample 14 is placed in the container 12. Thecontainer 12 is then vibrated by the shaker 16 so that the blood sample14, which is initially in a liquid state, is vibrating in a linearsloshing mode. A liquid typically vibrates near its first fundamentalnatural frequency in a sloshing mode, which can be defined as theswinging of the entire mass of the liquid in a container, hence theanalogy to a pendulum. The amplitude of the sloshing reaches maximumwhen the blood sample 14 is vibrated at its fundamental naturalfrequency. Thus, to initially excite the blood sample 14 to resonance,the shaker 16 vibrates the container 12 at or very near the fundamentalnatural frequency of the blood sample 14. Furthermore, the shaker 16vibrates the container 12 at or very near the fundamental naturalfrequency of the blood sample 14 as this frequency changes throughoutthe hemostasis and possibly lysis processes.

One of ordinary skill in the art will readily appreciate the numerousmethods by which the shaker 16 can vibrate the container 12 at or nearthe fundamental natural frequency of the blood sample 14 throughout thehemostasis and lysis processes. However, in the disclosed example, thecontainer 12 is initially vibrated at a frequency below the fundamentalnatural frequency of the blood sample 14. The frequency is thenincreased in small steps, and concurrently, the resulting displacementamplitudes of the blood sample 14 are measured. As the frequency ofvibration of the container 12 increases to near the blood sample'sfundamental natural frequency, the displacement amplitude of the bloodsample 14 will dramatically increase. The displacement amplitude of theblood sample 14 will reach maximum at its fundamental natural frequency.Thus, monitoring the displacement amplitude of the blood sample 14 for amaximum provides a value for the fundamental natural frequency of theblood sample 14 when that maximum is reached.

As the hemostasis process continues, the foregoing method of finding thefundamental natural frequency of the blood sample 14 is repeated. Themeasured fundamental natural frequencies of the blood sample 14 whenplotted vs. time result in a curve 30 similar to that shown in FIG. 2.Curve 30 is typically represented with its mirror image relative to thex-axis, which is shown as curve 31. The shape of the curve 30 isindicative of blood hemostasis characteristics. The x-axis 32 representstime, while the y-axis 34 represents the fundamental natural frequencyof the blood sample 14 during the hemostasis and lysis processes. One ofordinary skill in the art will appreciate that since frequency of theblood sample 14 is proportional to the modulus of elasticity of theblood sample 14, the y-axis also represents the changes in the modulusof elasticity of the blood sample 14 during hemostasis and lysisprocesses.

One of ordinary skill in the art will readily appreciate that the sizeof the frequency step by which the vibration frequency of the container12 is increased or decreased during testing will affect how quickly andefficiently the fundamental natural frequency of the blood sample 14 ispinpointed. For instance, a very large frequency step may not provide adetailed frequency resolution to locate a near accurate measure of thefundamental natural frequency of the blood sample 14. On the other hand,a very small frequency step may not provide a rapid approach topinpointing the fundamental natural frequency of the blood sample 14.Accordingly, in order to find the fundamental natural frequency of theblood sample within the frequency range by which the container 12 isvibrated, it may be necessary to search for the fundamental naturalfrequency of the blood sample 14 by changing the frequency step and/oradding or subtracting the frequency step from the vibration frequency ofthe container 12 in a methodical manner. Numerous mathematicalalgorithms and methods are well known to those of ordinary skill in theart, by which the frequency step can be methodically varied to provide arapid pinpointing of a peak in amplitude of oscillation of the bloodsample 14.

One of ordinary skill in the art can use other well known methods forfinding the fundamental natural frequency of the blood sample throughoutthe hemostasis and lysis processes. For example, displacing thecontainer 12 with a frequency function that emulates white noise havingfrequency components near or equal to the fundamental naturalfrequencies of the blood sample 14 throughout the hemostasis and lysisprocesses can excite the blood sample 14 to a resonant state. Whitenoise is a frequency function that includes frequency componentsselected within a range of frequencies. Because the blood sample willrespond with resonant excitation to a frequency that is equal or nearits fundamental natural frequency, a white noise having such a frequencycomponent will excite the blood sample 14 to a resonant state. One ofordinary skill in the art will readily appreciate that well knownmethods such as Fourier Frequency Analysis can be utilized to find thefundamental frequency of the blood sample 14 after being excited bywhite noise.

An exemplary device employing the foregoing method of determininghemostasis characteristics of a blood sample 14 will now be described.Referring to FIG. 1, the shaker 16 displaces the container 12 to excitethe blood sample 14 to resonant vibration. Generally, the shaker 16 is adevice capable of oscillating the container 12 with a desired frequencyand amplitude. One of ordinary skill in the art will appreciate thenumerous devices by which an object can be oscillated. In the disclosedexample, the shaker 16 is a dipcoil, which is similar to a voice coil ofa speaker. In other words, the shaker 16 includes an electromagnet thatoscillates relative to a stationary permanent magnet by having itscurrent driven by an electrical signal. The shaker 16 may be connectedeither directly or with a connecting link 36 to the container 12. Theconnecting link 36 transfers the motion created by the shaker 16 to thecontainer 12. As is well known to those of ordinary skill in the art,characteristics of the electrical signal, i.e., voltage, current,direction of current, etc., determine the characteristics of theoscillatory motion of the shaker 16. Accordingly, the shaker 16 candisplace the container 12 with any desired amplitude and frequencywithin the operational limits of the shaker 16.

The container 12 holds the blood sample 14 during the excitation of theblood sample 14. The container 12 may be any shape or size. However, theshape and size of the container may affect the operation of the analyzer10, because the container 12 acts as a resonator. The larger thecontainer 12, the lower the natural frequency of the blood sample 14will be. Furthermore, the container 12 cannot be too small so that ameniscus effect is produced due to the surface tension in the bloodsample 14. Conversely, if the container 12 is too large, a large bloodsample 14 will be needed for the analysis in the analyzer 10, which maynot be medically acceptable.

An exemplary container 12 is shown in FIG. 3. The container 12 has alower portion 40 and an upper portion 42. The lower portion 40 and theupper portion 42 are generally rectangular. The upper portion 42 has alarger width, a larger length, and a smaller depth than the lowerportion 40, so as to provide an internal step 44. The container 12 alsoincludes a lid 46 that is sealably attached to the top of the uppersection 40. The container 12 includes a port 48 for receiving a bloodsample 14. To reduce the meniscus effect of the blood sample 14 whenplaced in the container 12, the lower portion 40 is filled with theblood sample up to where the upper portion 42 begins. Accordingly, thevolume of the blood sample 14 is substantially equal to the volume ofthe lower portion 40.

To prevent the blood sample 14 from evaporating during testing and toprevent contamination thereof, the port 48 may be self sealing. Forexample, the port 48 may be constructed from rubber or silicon so thatwhen a syringe needle is inserted therein, the rubber or siliconresiliently surrounds the syringe needle to substantially seal the portduring the injection of the blood sample 14 into the container 12. Whenthe needle is withdrawn from the port 48, resilience of the rubber orthe silicon substantially re-seals the hole created by the needle. Toprevent evaporation of the blood sample 14 and any reaction the bloodsample may have by being exposed to air, the container 12 can bepre-filled or pressurized with an inert gas, such as Helium.Alternately, the air in the container can be removed to provide a vacuuminside the container 12. One of ordinary skill in the art will recognizethat the pressure in the container 12 has minimal to no effect on thefundamental natural frequency of the blood sample 14. In the exampledisclosed herein, the container 12 is safely disposable and can besafely discarded after each use. The disposability of the container 12ensures that the blood sample 14 is safely handled during testing andsafely discarded after testing. In addition, the disposable container 12can be manufactured to be completely sealed and only provide accessthereto by the port 48. Thus, the disposability of the container 12,combined with the container 12 being completely sealed, ensure that theblood sample 14 is not exposed to air (i.e., to prevent the drying ofthe surface of the blood sample 14) or any other contaminants, andfurthermore, ensure safety in handling and disposing of the blood sample14 before, during, and after testing.

The analyzer 10 includes a slot (not shown) to receive the container 12.One of ordinary skill in the art will readily appreciate that thecontainer 12 may be inserted in and removed from the slot in any mannerdesirable. However, to provide easy insertion and removal of thecontainer 12 from the analyzer 10, the container 12 may include a handle(not shown) that can be held by a user for insertion and removal of thecontainer 12 to and from the analyzer 10, respectively.

To measure oscillations of the blood sample 14 as a result of thedisplacement of the container 12, a fixed electromagnetic source 60emits a beam 62 toward the blood sample 14. As shown in FIG. 1, thesource 60 may be part of the sensor 18 (i.e., an active sensor).Alternatively, the source 60 and a sensor 66 (i.e., a passive sensor)can be independent devices. The beam 62 is detected by the sensor 18after being reflected from the surface of the blood sample 14. Thecharacteristics of the beam after being reflected from the surface ofthe blood sample 14 are indicative of the movement of the blood sample14 in response to displacements of the container 12.

One of ordinary skill in the art will appreciate that theelectromagnetic beam of the source 60 may be produced by any emissionwithin the electromagnetic spectrum so long as the beam 62 can reflectfrom the surface of the blood sample 14, and the beam's characteristicsafter reflecting from the surface of the blood sample 14 indicate themovement of the blood sample 14.

In the disclosed example, the source 60 is a fixed LED (Light EmittingDiode) source that directs a beam 62 towards the blood sample 14. Thebeam 62 is then reflected from the surface of the blood sample 14.Accordingly, the container 12 has an optically transparent portion sothat the beam 62 and its reflection 64 can enter and exit the container12, respectively. In the disclosed example, the lid 46 is transparent tolight. One of ordinary skill in the art will recognize that the lid 46,although transparent, will itself reflect some of the light in the beam62. To reduce the reflection of light from the lid 46, ananti-reflective coating may be applied to the lid 46. Suchanti-reflective coatings are well known to those of ordinary skill inthe art as they are applied to a variety of optical devices, such aseyeglasses, telescopes, cameras, etc. Although most liquids are highlytransparent to light, the surface of blood forms a highly reflectivesurface so that most of the beam 62 is reflected from the surface of theblood sample 14.

Referring to FIG. 4, the displacements of the blood sample 14 relativeto a rest position are shown with dashed lines 70 having an angle δ.Accordingly, the displacement of the blood sample 14 changes the angleof the reflection 64 of the beam 62 by the same angle δ. The sensor 18intercepts the reflection 64 of the beam 62 from the surface of theblood sample 14 and produces an electric signal indicative of thedisplacement of the blood sample 14. In the disclosed example, thesensor 18 includes a plurality of photo diodes that collectively detectthe displacement of the reflection of the beam 64. The outputs of thediodes are measured differentially so that peaks in the displacement ofthe blood sample 14, which are indicative of resonance, can beidentified.

In others example of the present disclosure, the vibrations in the bloodsample 14 may be measured by a number of other devices. In one example,acoustic sensors (not shown) disposed in the container 12 candifferentially measure the distance from the surface of the blood sample14 to the sensor, which is indicative of the vibration in the bloodsample 14. In another example, electrodes (not shown) arranged in thecontainer 12 function as either a capacitive or resistive bridge (i.e.,a Wheatstone bridge). The voltage differential of the capacitors or theresistors is indicative of the vibrations of the blood sample 14. In yetanother example, two photo diodes (not shown) can be placed on aninterior wall of the container near the surface of the blood sample 14.As the blood sample 14 vibrates, it partially or fully obscures one orboth of the diodes (i.e., preventing light from reaching the diodes).Accordingly, the outputs of the diodes are measured differentially sothat peaks in the displacement of the blood sample 14, which areindicative of resonance, can be identified

One of ordinary skill in the art will appreciate the numerous methodsand devices that can be used for driving the shaker 16 and analyzing thesignals from the sensor 18 for determining the hemostasischaracteristics of the blood sample 14. For instance, as shown in FIG.5, the blood hemostasis analyzer 10 can include an internal computingdevice 80 that includes the necessary hardware and software to drive theshaker 16 independently or in response to signals from the sensor 18.Furthermore, the internal computing device 80 can analyze the signalsfrom the sensor 18 to determine the fundamental natural frequencies ofthe blood sample 14 during hemostasis. As described in the foregoing,such an analysis will yield data for constructing the curves 30 andother data regarding the hemostasis characteristics of the blood sample14. In another example as shown in FIG. 6, the analyzer 10 can include amemory device 82 for storing the data from the sensor 18 for lateranalysis by an external computing device 84. The shaker 10 can be drivenby a predetermined method stored in the memory device 82, or by theexternal computing device 84. In yet another example shown in FIG. 7,the analyzer 10 does not include any internal memory or computingdevice. During testing, the analyzer 10 is in continuous and real-timecommunication with an external computing device 86 (e.g., laptop,personal digital assistant, desktop computer, etc.). The externalcomputing device 86 drives the shaker 16 and receives signals fromsensor 18 to determine the hemostasis characteristics of the bloodsample 14 as described in the foregoing. One of ordinary skill in theart will appreciate that numerous other well known methods, algorithmsand devices can be utilized to drive the shaker 16, independently or inresponse to signals from the sensor 18, and determine blood hemostasischaracteristics from the sensor signals. Furthermore, the determinedblood hemostasis characteristics can be conveyed to a user by a varietyof well known methods and devices, such as displaying data on a displayscreen, or printing the results on paper.

One of ordinary skill in the art will appreciate that the foregoinggeneralized device is very rugged and not easily susceptible to damagefrom being mishandled. The disclosed device has a very small number ofmoving parts or parts that are breakable. Furthermore, the simplicity ofthe disclosed device provides for quick replacement of a defective partwhen necessary.

Ambient vibrations or seismic noise near the analyzer 10 can disturb orinfluence the blood hemostasis analysis. Accordingly, the analyzer 10can include a vibration filtering device onto which the analyzer 10 ismounted. In a first example as shown in FIG. 8, the vibration filteringdevice is a hook 90, from which the analyzer 10 is suspended by a cable92. In effect, the analyzer 10 is suspended from the hook 90 in apendulum-like manner. Seismic noise or ambient vibration in a wide rangeof frequencies is dissipated through the hook 90 and the cable 92 priorto reaching the analyzer 10. One of ordinary skill in the art willappreciate that any wire that is connected to the analyzer 10 for poweror communication purposes can be carried by the cable 92 so as to notexternally influence the motion of the analyzer 10 (e.g., hanging wirescontacting other objects). In a second example as shown in FIG. 9, theseismic filtering device is a platform 100 that rests on a number oflegs 102. In effect, the platform 100 is an inverted pendulum. Inapplication, the analyzer 10 is placed on the platform 100 so that anyambient vibration or seismic noise within a wide frequency range isdissipated through the platform 100 prior to reaching the analyzer 10.One of ordinary skill in the art will appreciate many other ways ofisolating noise, including use of vibration absorbing foams, springsuspension and the like.

Although certain apparatus constructed in accordance with the teachingsof the invention have been described herein, the scope of coverage ofthis patent is not limited thereto. On the contrary, this patent coversall examples of the teachings of the invention fairly falling within thescope of the appended claims either literally or under the doctrine ofequivalents.

1. An apparatus for measuring hemostasis comprising: a. a container adapted to hold a blood sample, the container including a portion transparent to an emission from a sensor; b. a shaker adapted to displace the container in order to cause a resonant excitation of the blood sample, the blood sample being excited to a resonant state; and c. the sensor adapted to determine a movement of the blood sample corresponding to the resonant excitation of the blood sample within the container responsive to the displacement of the container by the shaker by generating the emission and directing the emission toward the blood sample through the portion; d. wherein data from the sensor is indicative of the resonant state of the blood sample and the shaker is configured to displace the container at a displacement frequency and configured to vary the displacement frequency responsive to changes in the resonant state of the blood sample.
 2. An apparatus according to claim 1, further comprising an analyzer coupled to the sensor to receive the data from the sensor, the analyzer being adapted to derive a hemostasis characteristic of the blood sample based upon the data from the sensor.
 3. An apparatus according to claim 1, wherein the shaker is configured to displace the container with a white noise frequency function.
 4. An apparatus according to claim 1, wherein the container includes a self-sealing port for receiving the blood sample.
 5. An apparatus according to claim 1, wherein the container is a sealed container.
 6. An apparatus according to claim 1, wherein the container is safely disposable.
 7. An apparatus according to claim 1, wherein the container comprises a first portion connected to a larger second portion, wherein the blood sample fills the first portion.
 8. An apparatus according to claim 1, wherein the sensor is an optical sensor.
 9. An apparatus for measuring hemostasis comprising: a. a slot for receiving a container having therein a blood sample, wherein a portion of the container is transparent to an emission from a sensor; b. a shaker adapted to displace the container in order to cause an excitation of the blood sample, the blood sample being excited to a resonant state; c. the sensor adapted to determine a movement of the blood sample within the container responsive to the displacement of the container by the shaker by generating the emission and directing the emission toward the blood sample through the portion; and d. an analyzer coupled to the sensor to receive data from the sensor, the analyzer being adapted to derive a hemostasis characteristic of the blood sample based upon the data from the sensor; e. wherein data from the sensor is indicative of the resonant state of the blood sample and the shaker is configured to displace the container at a displacement frequency and configured to vary the displacement frequency responsive to changes in the resonant state of the blood sample.
 10. An apparatus according to claim 9, wherein the shaker is configured to displace the container with a white noise frequency function. 